1. Field of the Invention
The present invention relates to antidotes for neurotoxins. More particularly, the invention relates to cyanide antidotes.
2. Brief Description of the Related Art
Neurotoxins damage or poison the central nervous system of mammals. An example of a neurotoxin is hydrogen cyanide. Inhalation or digestion of cyanide compounds may cause histotoxic hypoxia in tissue of the central nervous system as cyanide interferes with the performance of the cytochrome oxidase system thereby inhibiting the efficiency of oxygen transport to the tissues. Common cyanide compounds include hydrogen cyanide gas, cyanogen chloride gas, and crystalline solids such as potassium cyanide and sodium cyanide. The ease of delivery of these agents (especially gaseous cyanides) allow them to been used as an attack agent in chemical warfare.
Therapeutic attempts to counteract cyanide poisoning have been developed to inhibit the toxic effects of cyanide. For example, oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydyoxocobalamin, dicobalt EDTA, garlic extracts, disulfides, sodium pyruvate, alpha-keto-glutaric acid, aqueous solutions of ferrous sulfate in a citric acid sodium carbonate solution have been for cyanide detoxification.
U.S. Pat. No. 4,565,311 to Sarnoff, which is incorporated herein by reference, describes as an antidote for cyanide poisoning injectable hydroxylamine hydrochloride. This is followed by treatment with thiosulfate. The hydroxylamine hydrochloride can also be employed as a respiratory stimulant in treating other illnesses.
Many disulfides have been tested as antidotes for cyanide intoxication. Zottola et al. in “Disulfides as Cyanide Antidotes: Evidence for a New In Vivo Oxidative Pathway for Cyanide Detoxification.” Chemical Research Toxicology, 2009, 22, pp. 1948-1953, which is incorporated herein by reference, describes the conversion of cyanide to thiocyanate in the presence of the enzyme rhodanese. Rhodanese is an enzyme found primarily in the mitochondria. In a mammal, rhodanese is thought to be responsible for the conversion of cyanide to thiocyanate (SCN). Thiocyanate is then excreted by the kidney. Oxidized sulfur species such as sodium thiosulfate have been shown to be effective in vitro donors for rhodanese, however sodium thiosulfate in vivo efficacy is highly limited due to its limited cell penetration capability to reach the endogenous rhodanese. Thus, more effective sulfur analogs are desired.
Presently cyanide antidotes require intravenous injections with special trained personnel. Thus, the administration of the antidote is not efficient. As such, more efficient antidotal cyanide systems are desired.